Co-occurring conditions in Down syndrome: Findings from a clinical database.

Individuals with Down syndrome (DS) experience a range of medical and neurodevelopmental conditions, necessitating systematic study of their occurrence and impact on neurodevelopmental outcomes. We describe the prevalence and relationships of medical, neurodevelopmental (ND), and mental health (MH) conditions in children with DS. We created a prospective clinical database of individuals with DS, integrated into the workflow of a specialty Down Syndrome Program at a specialty pediatric referral hospital. Conditions were collected through caregiver- and clinician report at clinical visits (N = 599). We calculated frequencies of medical, ND, and MH conditions and then assessed the relationship between medical, ND, and MH conditions using frequencies and comparative statistics. The most frequent co-occurring conditions were vision (72.5%), ear/hearing (71.0%), gastrointestinal (61.3%), respiratory (45.6%), and feeding (33.6%) problems, with variation in frequency by age. ND and MH conditions were reported in one quarter, most commonly autism spectrum disorder and attention-deficit/hyperactivity disorder. Those with ND and MH conditions had greater frequency of medical conditions, with highest rates of vision, ear/hearing, and gastrointestinal issues, and CHD. Systematically collected clinical data in a large cohort of children with DS reveals high prevalence of several co-occurring medical, ND, and MH conditions. Clinical care requires an understanding of the complex relationship between medical conditions and neurodevelopment.

Development and implementation of a longitudinal clinical database for down syndrome in a large pediatric specialty clinic: Methodology and feasibility.

Down syndrome (DS) is a complex condition associated with multiple medical, developmental, and behavioral concerns. A prospective, longitudinal clinical database was integrated into a specialty Down Syndrome Program, with the goals of better understanding the incidence, course, and impact of co-occurring medical, neurodevelopmental, and mental health conditions in DS. We describe the process of developing the database, including a systematic approach to data collection and database infrastructure, and report on feasibility, challenges, and solutions of initial implementation. Between March 2018 and November 2021, data from 842 patients (ages 4.8 months to 26 years) was collected. Challenges included caregiver form completion as well as time and personnel required for successful implementation. With full integration into clinical visit flow, the database proved to be feasible. The database enables identification of patterns of development and health throughout the lifespan and it facilitates future data sharing and collaborative research to advance care.

Topical Review: Transitional Services for Teens and Young Adults With Attention-Deficit Hyperactivity Disorder: A Process Map and Proposed Model to Overcoming Barriers to Care.

Objective: To provide a topical review of the personal vulnerabilities and systemic barriers facing transitional age young adults with attention-deficit hyperactivity disorder (ADHD), followed by a proposed model for overcoming those barriers. Methods: Drawing from a growing, but limited, literature on the topic, we outline a process map for identifying and troubleshooting barriers to care in this at-risk population. Results: Young adults with ADHD frequently lack the organizational skills, time management, prioritization, and persistence to manage their health care at an expected level of adult independence. These difficulties are compounded by a health-care system that has less time or fewer resources for supporting young adult patients. Conclusions: Recommendations for easing the transition from pediatric to adult care for late adolescents with ADHD include heavily leveraging the doctor-patient relationship, and capturing the young adult's attention through technologies that already absorb them.

Dietary docosahexaenoic acid supplementation in children with autism.

OBJECTIVE: The aim of the study was to determine whether docosahexaenoic acid (DHA) supplementation improves the behavior of children with autism. METHODS: A group of 3- to 10-year-old children with autism were randomized in a double-blind fashion to receive a supplement containing 200 mg of DHA or a placebo for 6 months. The parents and the investigator completed the Clinical Global Impressions-Improvement scale to rate changes in core symptoms of autism after 3 and 6 months. The parents completed the Child Development Inventory and the Aberrant Behavior Checklist, and both parents and teachers completed the Behavior Assessment Scale for Children (BASC) at enrollment and after 6 months. RESULTS: A total of 48 children (40 [83%] boys, mean age [standard deviation] 6.1 [2.0] years) were enrolled; 24 received DHA and 24 placebo. Despite a median 431% increase in total plasma DHA levels after 6 months, the DHA group was not rated as improved in core symptoms of autism compared to the placebo group on the CGI-I. Based on the analysis of covariance models adjusted for the baseline rating scores, parents (but not teachers) provided a higher average rating of social skills on the BASC for the children in the placebo group compared to the DHA group (P = 0.04), and teachers (but not parents) provided a higher average rating of functional communication on the BASC for the children in the DHA group compared to the placebo group (P = 0.02). CONCLUSIONS: Dietary DHA supplementation of 200 mg/day for 6 months does not improve the core symptoms of autism. Our results may have been limited by inadequate sample size.

Persistence of Autism Spectrum Disorder From Early Childhood Through School Age.

Importance: While the prevalence of autism spectrum disorder (ASD) continues to increase and early diagnosis is emphasized, there is limited information on outcomes for children diagnosed with ASD in early childhood using contemporary diagnostic criteria. Objectives: To determine the frequency with which children who are clinically diagnosed with ASD at 12 to 36 months of age continue to meet diagnostic criteria for ASD at 5 to 7 years of age and to evaluate whether baseline child-specific and demographic characteristics and receipt of interventions are associated with ASD persistence. Design, Setting, and Participants: In this natural history cohort study, children who received a clinical ASD diagnosis at 12 to 36 months of age underwent a research diagnostic assessment at 5 to 7 years of age. Research assessments occurred from August 14, 2018, to January 8, 2022. Intervention: Children received community-based interventions, and parents provided details about interventions received. Main Outcomes and Measures: The main outcome was persistence of ASD diagnosis based on current functioning. An experienced research psychologist assigned an ASD diagnosis (present or absent) according to criteria from the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) after the research assessment. The research assessment included administration of the Autism Diagnostic Observation Schedule-2, Autism Diagnostic Interview-Research, and a cognitive measure. Results: Of the 213 participants diagnosed with ASD at initial clinical assessment (mean [SD] age, 24.6 [3.9] months; 177 boys [83.1%]), 79 (37.1%) did not continue to meet diagnostic criteria for ASD (nonpersistent ASD) at research assessment (mean [SD] age, 74.3 [7.1] months). All children with nonpersistent ASD had IQ of at least 70, while there was a bimodal distribution of IQ for those with persistent ASD (46 with IQ <70 and 88 with IQ ≥70). All children received some interventions, and 201 (94.4%) received ASD-specific intervention, mostly applied behavioral analysis. In a multilevel logistic regression model, the only variables associated with increased odds of being in the nonpersistent ASD group at 6 years of age were higher baseline adaptive skills (b coefficient = -0.287 [SE, 0.108]) and female sex (b = 0.239 [SE, 0.064]). Conclusions and Relevance: The findings of this cohort study suggest that among toddlers diagnosed with ASD, baseline adaptive function and sex may be associated with persistence of ASD.

Childhood ADHD is strongly associated with a broad range of psychiatric disorders during adolescence: a population-based birth cohort study.

BACKGROUND: To evaluate associations between attention-deficit/hyperactivity disorder (ADHD) and comorbid psychiatric disorders using research-identified incident cases of ADHD and population-based controls. METHODS: Subjects included a birth cohort of all children born 1976-1982 remaining in Rochester, MN after age five (n = 5,718). Among them we identified 379 ADHD incident cases and 758 age-gender matched non-ADHD controls, passively followed to age 19 years. All psychiatric diagnoses were identified and abstracted, but only those confirmed by qualified medical professionals were included in the analysis. For each psychiatric disorder, cumulative incidence rates for subjects with and without ADHD were estimated using the Kaplan-Meier method. Corresponding hazard ratios (HR) were estimated using Cox models adjusted for gender and mother's age and education at the subject's birth. The association between ADHD and the likelihood of having an internalizing or externalizing disorder was summarized by estimating odds ratios (OR). RESULTS: Attention-deficit/hyperactivity disorder was associated with a significantly increased risk of adjustment disorders (HR = 3.88), conduct/oppositional defiant disorder (HR = 9.54), mood disorders (HR = 3.67), anxiety disorders (HR = 2.94), tic disorders (HR = 6.53), eating disorders (HR = 5.68), personality disorders (HR = 5.80), and substance-related disorders (HR = 4.03). When psychiatric comorbidities were classified on the internalization-externalization dimension, ADHD was strongly associated with coexisting internalizing/externalizing (OR = 10.6), or externalizing-only (OR = 10.0) disorders. CONCLUSION: This population-based study confirms that children with ADHD are at significantly increased risk for a wide range of psychiatric disorders. Besides treating the ADHD, clinicians should identify and provide appropriate treatment for psychiatric comorbidities.

Male and Female Toddlers with DSM-5 Autism Spectrum Disorder have Similar Developmental Profiles and Core Autism Symptoms.

Compare developmental profiles and core ASD symptom manifestation between male and female toddlers with DSM-5 ASD. Retrospective record review of 500 toddlers (79% male) at time of ASD diagnosis. There were no differences in developmental functioning between males and females. When adjusting for multiple comparisons, sex differences were only noted for sensory seeking behavior occurring at a higher frequency in females. Overall, there were no significant differences in demographic characteristics, developmental functioning, or manifestation of core ASD symptoms between males versus female toddlers at the time of DSM-5 ASD diagnosis.

Recalled Experiences of Bullying and Victimization in a Longitudinal, Population-Based Birth Cohort: The Influence of ADHD and Co-Occurring Psychiatric Disorder.

OBJECTIVE: To describe bullying experiences throughout childhood of people with and without childhood ADHD and co-occurring learning and psychiatric disorders from a population-based birth cohort. METHODS: In a secondary data analysis of 199 childhood ADHD cases and 287 non-ADHD referents (N = 486), reported experiences of peer interactions during elementary, middle, or high school were classified as "bully," "victim," "neither," or "both." Associations were assessed with multinomial logistic regression. RESULTS: Adjusted for male sex, the odds of classification as victim-only, victim/bully, or bully- only (vs. neither) were 3.70 (2.36-5.81), 17.71, and 8.17 times higher for childhood ADHD cases compared to non-ADHD referents. Victim-bullies (62.5%) and bullies (64.3%) had both childhood ADHD and other psychiatric disorders versus 38.4% of victims-only and 17.3% of those classified as "neither." CONCLUSION: The list of serious lifetime consequences of having ADHD also includes bullying. We offer future research directions for determining potential causal pathways.

Children With ADHD Are at Risk for a Broad Array of Adverse Adult Outcomes That Cross Functional Domains: Results From a Population-Based Birth Cohort Study.

OBJECTIVE: To identify patterns ("classes") of outcomes for adults with and without childhood ADHD. METHOD: Subjects were 232 childhood ADHD cases and 335 non-ADHD referents from a 1976 to 1982 birth cohort. We used latent class analyses to identify classes based on a broad array of adult psychosocial outcomes and determined the proportion of subjects with childhood ADHD within each class. RESULTS: A three class solution provided optimal model fit; classes were termed "good," "intermediate," and "poor" functioning. Subjects with childhood ADHD comprised 62.8% of the "poor," 53.5% of the "intermediate," and 24.9% of the "good" functioning class. The "poor" functioning class was distinguished by increased likelihood of legal trouble and substance use disorders and included more individuals with childhood ADHD and psychiatric disorder than the "intermediate" class (45.5% vs. 30.6%). CONCLUSION: Children with ADHD are at risk for adverse adult outcomes in multiple domains and co-morbid childhood psychiatric disorders increase risk.

Identifying Subgroups of Toddlers with DSM-5 Autism Spectrum Disorder Based on Core Symptoms.

The objective of this study was to identify subgroups of toddlers with DSM-5 ASD based on core ASD symptoms using a person-based analytical framework. This is a retrospective study of 500 toddlers (mean age 26 months, 79% male) with DSM-5 ASD. Data were analyzed using latent class analyses in which profiles were formed based on ASD symptomatology. Social communication (SC) symptoms favored a three-class solution, while restricted/repetitive behaviors (RRBs) favored a two-class solution. Classes with higher consistency of SC deficits were younger, with lower developmental functioning. The class with more RRBs was older, with higher functioning. If confirmed in other populations, these classes may more precisely characterize subgroups within the heterogeneous group of toddlers at time of ASD diagnosis.

Developing the Evidence-Grading Tools and Process for the Complex Attention-Deficit/Hyperactivity Disorder Guideline.

Clinical practice guidelines (CPGs) rely on a robust assessment of the quality of evidence supporting guideline recommendations. For the Society for Developmental and Behavioral Pediatrics (SDBP) CPG for the Assessment and Treatment of Children and Adolescents with Complex Attention-Deficit Hyperactivity Disorder (ADHD), the nature of the evidence and resource constraints led the guideline panel to develop an innovative, yet rigorous, approach to evidence grading. This study will (1) describe the challenges of evidence grading for the SDBP Complex ADHD Guideline; (2) discuss the rationale, process, and tools developed to conduct evidence grading; and (3) report on the experiences and readiness of the volunteer reviewers with diverse background in research methodology to conduct evidence grading. This evidence review process may serve as an example of approaches that can be used by other groups tasked with evaluating the evidence in support of new CPGs.

Pathogenic Yield of Genetic Testing in Autism Spectrum Disorder.

BACKGROUND AND OBJECTIVES: Genetic testing is recommended for individuals with autism spectrum disorder (ASD). Pathogenic yield varies by clinician and/or patient characteristics. Our objectives were to determine the pathogenic yield of genetic testing, the variability in rate of pathogenic results based on subject characteristics, and the percentage of pathogenic findings resulting in further medical recommendations in toddlers with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of ASD. METHODS: We conducted a retrospective chart review of 500 toddlers, 18 to 36 months, diagnosed with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ASD (mean age: 25.8 months, 79% male). Subject demographics, medical and neuropsychological characteristics, and genetic test results were abstracted. Genetic results were divided into negative or normal, variants of unknown significance, and pathogenic. Subject characteristics were compared across results. Manual chart review determined if further recommendations were made after pathogenic results. RESULTS: Over half of subjects (59.8%, n = 299) completed genetic testing, and of those, 36 (12.0%) had pathogenic findings. There were no significant differences in Bayley Scales of Infant Development cognitive (P = .112), language (P = .898), or motor scores (P = .488) among children with negative or normal findings versus a variant of unknown significance versus pathogenic findings. Medical recommendations in response to the genetic finding were made for 72.2% of those with pathogenic results. CONCLUSIONS: Our findings reinforce the importance of genetic testing for toddlers diagnosed with ASD given the 12% yield and lack of phenotypic differences between subjects with and without pathogenic findings. The majority of pathogenic results lead to further medical recommendations.

Society for Developmental and Behavioral Pediatrics Clinical Practice Guideline for the Assessment and Treatment of Children and Adolescents with Complex Attention-Deficit/Hyperactivity Disorder.

Attention-deficit/hyperactivity disorder (ADHD) is the most common childhood neurodevelopmental disorder and is associated with an array of coexisting conditions that complicate diagnostic assessment and treatment. ADHD and its coexisting conditions may impact function across multiple settings (home, school, peers, community), placing the affected child or adolescent at risk for adverse health and psychosocial outcomes in adulthood. Current practice guidelines focus on the treatment of ADHD in the primary care setting. The Society for Developmental and Behavioral Pediatrics has developed this practice guideline to facilitate integrated, interprofessional assessment and treatment of children and adolescents with "complex ADHD" defined by age (<4 years or presentation at age >12 years), presence of coexisting conditions, moderate to severe functional impairment, diagnostic uncertainty, or inadequate response to treatment.

Early exposure to anesthesia and learning disabilities in a population-based birth cohort.

BACKGROUND: Anesthetic drugs administered to immature animals may cause neurohistopathologic changes and alterations in behavior. The authors studied association between anesthetic exposure before age 4 yr and the development of reading, written language, and math learning disabilities (LD). METHODS: This was a population-based, retrospective birth cohort study. The educational and medical records of all children born to mothers residing in five townships of Olmsted County, Minnesota, from 1976 to 1982 and who remained in the community at 5 yr of age were reviewed to identify children with LD. Cox proportional hazards regression was used to calculate hazard ratios for anesthetic exposure as a predictor of LD, adjusting for gestational age at birth, sex, and birth weight. RESULTS: Of the 5,357 children in this cohort, 593 received general anesthesia before age 4 yr. Compared with those not receiving anesthesia (n = 4,764), a single exposure to anesthesia (n = 449) was not associated with an increased risk of LD (hazard ratio = 1.0; 95% confidence interval, 0.79-1.27). However, children receiving two anesthetics (n = 100) or three or more anesthetics (n = 44) were at increased risk for LD (hazard ratio = 1.59; 95% confidence interval, 1.06-2.37, and hazard ratio = 2.60; 95% confidence interval, 1.60-4.24, respectively). The risk for LD increased with longer cumulative duration of anesthesia exposure (expressed as a continuous variable) (P = 0.016). CONCLUSION: Exposure to anesthesia was a significant risk factor for the later development of LD in children receiving multiple, but not single anesthetics. These data cannot reveal whether anesthesia itself may contribute to LD or whether the need for anesthesia is a marker for other unidentified factors that contribute to LD.

Anesthesia for cesarean delivery and learning disabilities in a population-based birth cohort.

BACKGROUND: Anesthetics administered to immature brains may cause histopathological changes and long-term behavioral abnormalities. The association between perinatal exposure to anesthetics during Cesarean delivery (CD) and development of learning disabilities (LD) was determined in a population-based birth cohort. METHODS: The educational and medical records of all children born to mothers residing in five townships of Olmsted County, Minnesota from 1976-1982 and remaining in the community at age 5 were reviewed to identify those with LDs. Cox proportional hazards regression was used to compare rates of LD between children delivered vaginally and via CD (with general or regional anesthesia). RESULTS: Of the 5,320 children in this cohort, 497 were delivered via CD (under general anesthesia n = 193, and regional anesthesia n = 304). The incidence of LD depended on mode of delivery (P = 0.050, adjusted for sex, birth weight, gestational age, exposure to anesthesia before age 4 yr, and maternal education). LD risk was similar in children delivered by vagina or CD with general anesthesia, but was reduced in children receiving CD with regional anesthesia (hazard ratio = 0.64, 95% confidence interval 0.44 to 0.92; P = 0.017 for comparison of CD under regional anesthesia compared to vaginal delivery). CONCLUSION: Children exposed to general or regional anesthesia during CD are not more likely to develop LD compared to children delivered vaginally, suggesting that brief perinatal exposure to anesthetic drugs does not adversely affect long-term neurodevelopmental outcomes. The risk of LD may be lower in children delivered by CD whose mothers received regional anesthesia.

Psychiatric Comorbidities Modify the Association Between Childhood ADHD and Risk for Suicidality: A Population-Based Longitudinal Study.

OBJECTIVE: The objective of this study was to evaluate the effect of psychiatric comorbidities on the association between childhood ADHD and suicidality among adults. METHOD: Subjects were recruited from a population-based birth cohort. Participating adult subjects with childhood ADHD and non-ADHD controls were administered a structured psychiatric interview to assess suicidality and psychiatric comorbidities. Associations were assessed using logistic regression. RESULTS: Compared with controls, ADHD cases were significantly more likely to meet criteria for suicidality. Subjects with childhood ADHD who met criteria for generalized anxiety disorder had a higher than expected risk of suicidality with an observed odds ratio of 10.94 (95% confidence interval [4.97, 24.08]) compared with an expected odds ratio of 4.86, consistent with a synergistic interaction effect. Significant synergistic interactions were also observed for hypomanic episode and substance-related disorders. CONCLUSION: Childhood ADHD is significantly associated with adult suicidal risk. Comorbidity between ADHD and some psychiatric disorders is associated with a higher suicidal risk than expected.

High-Functioning Autism, Severe Anxiety, and Bullying in a 26 Year Old.

CASE: Peter is a 26-year-old group home resident in Austria with a history of poor peer relationships, including being bullied, and previous diagnoses of attention-deficit hyperactivity disorder, Asperger syndrome, social anxiety, depression, and developmental coordination disorder. Consultation from our international neurodevelopmental team was requested for severe anxiety and avoidance of social interactions. He reported 4 or more spontaneous anxiety episodes per day. Anxiety triggers included returning to his group home from his vocational rehabilitation program each evening or returning to the group home after weekends at his parents' house. Each Sunday evening, in anticipation of returning to the group home, Peter engaged in tantrums, including screaming and throwing objects and suicidal threats without intent, but not direct aggression toward family members. He phoned his mother several times per day on weekdays.Peter's early history was significant for hyperactivity, impulsivity, aggression, and socially intrusive behavior; he repeated kindergarten and by first grade was characterized as motorically clumsy and "too much in [peers'] personal space." He played alone in kindergarten and had poor social boundaries; when older, he evidenced reduced social perception, and his family reported he did not notice when peers made fun of him. His language developed normally, but he had a "sophisticated style of speaking" and as an adult continued to have trouble understanding gestures, jokes, and social themes in movies.Between ages 7 and 11 years, Peter had been bullied and ostracized by male peers but did well academically, always got along well with adults, and preferred to play with girls. Exclusion by peers persisted through high school, at which time his independent functioning declined and he required his mother's assistance with organizing his materials. At age 15 years, Peter repeated a grade so that he could change classmates, and by the equivalent of his junior year, his grades deteriorated. He had several psychiatric admissions for depression and destructive outbursts (to avoid going to school) and was diagnosed with Asperger disorder. At age 18 years, Peter refused to return to school. He lived at home with his parents, only leaving the house to accompany them on errands, until placed in a group home for people with mental health disorders at age 20 years. At age 26 years, he is sharing a supported-living apartment with 2 young adults with chronic psychiatric disorders. He works in 3 highly structured sheltered workshops for a few hours each and becomes easily overwhelmed in unstructured situations and/or in situations in which he anticipates being reprimanded or letting someone down. Despite a strong interest in marine biology, anxiety prevents him from considering college.How would you proceed with diagnostic testing or intervention to help this young man?

Stimulant medication treatment of target behaviors in children with autism: a population-based study.

OBJECTIVE: This study provides detailed information about stimulant medication treatment for the target symptoms of hyperactivity, impulsivity, disinhibition, and inattention in children with autism. METHODS: In a previous study, 124 subjects fulfilling DSM-IV-based research criteria for autistic disorder were identified among all 0-21 year old residents of Olmsted County, MN from 1976-1997. For each of these 124 children with research-identified autism, information was abstracted on all prescribed psychopharmacological medications. RESULTS: Psychostimulants were used to treat 52.4% (N = 65) of the 124 subjects. The median total duration of psychostimulant treatment was 4.0 years. There were 398 episodes of psychostimulant treatment. Favorable responses were associated with 69.4% of treatment episodes. Of the 398 episodes of stimulant treatment, 16.8% were associated with a documented side effect. At least one side effect was experienced by 66% of the children. CONCLUSION: These results indicate that psychostimulants are commonly prescribed for children with autism, and suggest that these medications may improve the target symptoms of hyperactivity, impulsivity, disinhibition and inattention.

Comparing Methods to Determine Persistence of Childhood ADHD Into Adulthood: A Prospective, Population-Based Study.

OBJECTIVE: To compare the rate of persistence of ADHD into adulthood as determined by a norm-referenced versus non-norm-referenced diagnostic interview, and by standardized questionnaires. METHOD: Adults from a birth cohort, including research-identified childhood ADHD cases ( N = 232; Mage = 27.0 years; 167 males, 65 females) and controls ( N = 335; Mage = 28.6 years; 210 males, 125 females), were administered the M.I.N.I. International Neuropsychiatric Interview, the Murphy-Barkley Symptoms Checklist (MB), and the Wender Utah Rating Scale (WURS) Results: Among the childhood ADHD cases, 29.3% fulfilled criteria for adult ADHD using a norm-referenced approach to M.I.N.I. scoring, versus 13.8% using published M.I.N.I. criteria. Among participants meeting norm-referenced diagnostic criteria, 41.8% and 69.1% were classified as adult ADHD using the MB and WURS, respectively. CONCLUSION: A non-norm-referenced approach resulted in a significant underestimate of the rate of adult ADHD. Reliance on either of two adult ADHD questionnaires would have further reduced this estimate.